Hepatitis E virus (HEV) is an emerging enteric pathogen responsible for most
acute hepatitis worldwide. This dissertation presents data from studies conducted from
2001-2006 in the Matlab Health Research Center population under the International
Center for Diarrheal Disease Research, Bangladesh. These studies define the previously
unknown burden of HEV in rural Bangladesh and address gaps in HEV epidemiology.
This work begins with a literature review, focusing on the challenges presented by this
virus: the unexplained high case fatality in pregnancy, the absence of HEV in children,
the rapid deterioration of immunity, and recent evidence implicating some HEV
genotypes as zoonoses. The first study is a cross-sectional assessment of antibody
seroprevalence to three hepatitis viruses (B,C&E) in a representative random population
sample (n=1134). This study revealed a 22.5% seroprevalence of anti-HEV, 35.2% anti-
HBc and 1.5% anti-HCV. Anti-HEV seroprevalence peaked in the second/third decades
of life, as seen in India/Nepal. Male gender and outdoor employment were significantly
associated with seropositivity. The second study follows this baseline cohort
longitudinally for 18 months to determine HEV infection and disease rates. From 837
person-years (P-Y) of exposure, an incidence rate of 60.3/1000P-Y was estimated. Agespecific
seroincidence increased in subsequent 10-year categories, peaking at 41-50y.
Although clinical illness seemed infrequent, a disease:infection ratio as high as 49 per
100 (95%CI:31–73) was estimated. Third, an exploratory nested case control study
attempts to identify putative risk factors for sporadic hepatitis E disease. Over 22 months,
13 field workers used a morbidity-scoring algorithm to identify acute hepatitis-like illness
in their catchment population of 23,500. Finally, 46 confirmed HEV infections were
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compared to 134 sero-naïve age-matched controls. Cases were less likely to be <15y,
female or use unsanitary latrines in their homes. Outdoor employment, work outside the
home, and travel to a town/city emerged as risk factors. Unlike in previous studies, recent
contact with a “jaundice” patient and injection exposures were significant. These studies
establish that: HEV is endemic in rural Bangladesh; sporadic infections are frequent in
the absence of outbreaks; and, aside from classic hygiene risk factors, there may be other
pathways through which HEV is transmitted.